Amino Acid Residues 253 and 591 of the PB2 Protein of Avian Influenza Virus A H9N2 Contribute to Mammalian Pathogenesis

Author:

Mok Chris Ka Pun1,Yen Hui Ling1,Yu May Yan Mei1,Yuen Kit Man1,Sia Sin Fun1,Chan Michael Chi Wai1,Qin Gang2,Tu Wen Wei2,Peiris Joseph Sriyal Malik1

Affiliation:

1. Department of Microbiology, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong Special Administrative Region (SAR), People's Republic of China

2. Department of Pediatrics and Adolescent Medicine, LKS Faculty of Medicine, University of Hong Kong, Hong Kong SAR, People's Republic of China

Abstract

ABSTRACT We investigated the tropism, host responses, and virulence of two variants of A/Quail/Hong Kong/G1/1997 (H9N2) (H9N2/G1) with D253N and Q591K in the PB2 protein in primary human macrophages and bronchial epithelium in vitro and in mice in vivo . Virus with PB2 D253N and Q591K had greater polymerase activity in minireplicon assays, induced more tumor necrosis factor alpha (TNF-α) in human macrophages, replicated better in differentiated normal human bronchial epithelial (NHBE) cells, and was more pathogenic for mice. Taken together, our studies help define the viral genetic determinants that contribute to pathogenicity of H9N2 viruses.

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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